Differential regulation of antiviral T-cell immunity results in stable CD8(+) but declining CD4(+) T-cell memory

Emerging evidence indicates that CD8(+) and CD4(+) T-cell immunity is diffe rentially regulated. Here we have delineated differences and commonalities among antiviral T-cell responses by enumeration and functional profiling of eight specific CD8(+) and CD4(+) T-cell populations during primary, memory and recall responses. A high degree of coordinate regulation among all spe cific T-cell populations stood out against an approximately 20-fold lower p eak expansion and prolonged contraction phase of specific CD4(+) T-cell pop ulations. Surprisingly, although CD8(+) T-cell memory was stably maintained for life, levels of specific CD4(+) memory T cells gradually declined. How ever, this decay, which seemed to result from less efficient rescue from ap optosis, did not affect functionality of surviving virus-specific CD4(+) T cells. Our results indicate that CD4(+) T-cell memory might become limiting under physiological conditions and that conditions precipitating CD4(+) T- cell loss might compromise protective immunity even in the presence of unim paired CD8+ T-cell responses.